Biological Evaluation of Orthopedic Materials: An In Vitro Study Using Patient-Derived Human Samples

NCT07671521 | Not Yet Recruiting DMC

• 1 other identifier: RAISE
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The anterior cruciate ligament (ACL) is the primary stabilizer of the knee joint, and ACL injuries are highly prevalent, particularly among physically active and athletic individuals. Although ACL reconstruction is a well-established orthopedic procedure, significant challenges remain regarding biological integration between the graft and bone, which may negatively affect clinical outcomes. In recent years, advanced biomaterials and regenerative medicine approaches have gained increasing attention as potential strategies to enhance osteointegration and promote more physiological tissue healing. Before clinical application, these materials must undergo rigorous in vitro biological evaluation in accordance with international standards, particularly ISO 10993-5 for cytotoxicity assessment. The study will investigate cytotoxicity, cell viability, inflammatory responses, pro-fibrotic effects, and osteogenic potential using relevant human cell models. The regenerative effects of platelet-rich plasma (PRP), a source of growth factors, will also be evaluated. The biomaterials under investigation include a titanium alloy and polylactic acid (PLA), both widely used in orthopedic applications. The main objective is to demonstrate their biocompatibility, absence of cytotoxic, inflammatory, and pro-fibrotic effects, and their ability to support osteogenic processes and tissue integration. The findings will provide essential evidence for subsequent preclinical in vivo studies and future clinical translation.

Conditions

Cytotoxicity

Outcome Measures

Primary Outcomes (1)

• Cellular health parameters

  Cellular health parameters were assessed after 72 hours of exposure to the materials and compared with standardized control samples

  72 hours

Secondary Outcomes (3)

• Pro-inflammatory cytokines

  48 hours

• ROS

  48 hours

• Osteogenic potential

  28 days

Study Arms (3)

PTG

Subjects eligible among patients scheduled for primary total knee arthroplasty, in whom harvesting of the tibial plateau and/or femoral condyles and/or synovial tissue is planned

BMC

Concentrated bone marrow samples

PRP

Platelet-rich plasma samples

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects will be recruited among patients admitted to the IRCCS Istituto Ortopedico Rizzoli and scheduled for total knee arthroplasty for the treatment of chondral defects and/or undergoing regenerative infiltrative therapies with BMC and PRP. For the study, biological material obtained during the surgical removal of femoral condyles, tibial plateaus and synovial membranes, as well as during implantation of the prosthetic components, will be used. For BMC and PRP, only waste material not required for the surgical procedures will be collected. The recovery of such material will be performed during routine clinical practice by the medical staff of the Orthopaedic and Trauma Clinic II.

You may qualify if:

• Age 18-80 years, male or female Primary tricompartmental osteoarthritis Body Mass Index (BMI) \< 35 Kellgren-Lawrence grade III-IV osteoarthritis Written informed consent

You may not qualify if:

• Previous partial knee arthroplasty or cartilage repair/regenerative procedures Rheumatoid arthritis or chronic corticosteroid/immunosuppressive therapy Positive testing for HIV, HBV or HCV infection Concentrated bone marrow (BMC) samples
• Patients of both sexes providing written informed consent and presenting with the following characteristics:
• Age 18-70 years Medial compartment knee osteoarthritis (Kellgren-Lawrence grade II-III for \>4 months) Failure of ≥6 months of conservative treatment (NSAIDs/analgesics, hyaluronic acid, corticosteroid or PRP injections) Written informed consent
• Inability to provide informed consent Knee trauma within the previous 6 months Malignancy, rheumatic disease, uncontrolled diabetes, uncontrolled thyroid disorders Alcohol or drug abuse BMI \> 35 Intra-articular injections within the previous 6 months Knee surgery within the previous 12 months HIV, HBV or HCV positivity Platelet-rich plasma (PRP) samples
• Patients of both sexes with degenerative cartilage disease of the knee.
• Age 18-65 years Clinical signs and symptoms of knee cartilage degeneration Radiographic or MRI evidence of degeneration (Kellgren-Lawrence grade II-IV) Hemoglobin \> 11 g/dL Platelet count \> 150,000/mm³ No clinically relevant ECG abnormalities Written informed consent
• Rheumatoid arthritis or chronic corticosteroid/immunosuppressive therapy Uncontrolled diabetes Hematological disorders or anticoagulant/antiplatelet therapy Thyroid metabolic disorders Alcohol, drug or medication abuse NSAID use within 3 days prior to blood draw Cardiovascular disease contraindicating a 150 mL blood draw HIV, HBV or HCV positivity

Sponsors & Collaborators

• Stefano Zaffagnini: lead

Study Sites (1)

IRCCS Rizzoli Orthopedic Institute

Bologna, 40136, Italy

Location

Central Study Contacts

stefano zaffagnini

CONTACT

0516366075; stefano.zaffagnini@unibo.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Full Professor Medicine and Surgery, University of Bologna

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: June 26, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 26, 2026

Record last verified: 2026-06

Locations

IT (1)